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The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
15 Projects, page 1 of 2

  • Canada
  • 2012-2021
  • UK Research and Innovation
  • UKRI|BBSRC
  • OA Publications Mandate: No

10
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  • Funder: UKRI Project Code: BB/W010720/1
    Funder Contribution: 3,000 GBP
    Partners: UBC, IFR

    Canada

  • Funder: UKRI Project Code: BB/P02582X/1
    Funder Contribution: 30,612 GBP
    Partners: University of Aberdeen, SFU, MUN, UNIVERSITY OF VICTORIA

    Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

  • Funder: UKRI Project Code: BB/L007320/1
    Funder Contribution: 346,292 GBP
    Partners: NRC, University of Alberta, DuPont (Global), Max Planck, Cardiff University

    Oil crops are one of the most important agricultural commodities. In the U.K. (and Northern Europe and Canada) oilseed rape is the dominant oil crop and worldwide it accounts for about 12% of the total oil and fat production. There is an increasing demand for plant oils not only for human food and animal feed but also as renewable sources of chemicals and biofuels. This increased demand has shown a doubling every 8 years over the last four decades and is likely to continue at, at least, this rate in the future. With a limitation on agricultural land, the main way to increase production is to increase yields. This can be achieved by conventional breeding but, in the future, significant enhancements will need genetic manipulation. The latter technique will also allow specific modification of the oil product to be achieved. In order for informed genetic manipulation to take place, a thorough knowledge of the biosynthesis of plant oils is needed. Crucially, this would include how regulation of oil quality and quantity is controlled. The synthesis of storage oil in plant seeds is analogous to a factory production line, where the supply of raw materials, manufacture of components and final assembly can all potentially limit the rate of production. Recently, we made a first experimental study of overall regulation of storage oil accumulation in oilseed rape, which we analysed by a mathematical method called flux control analysis. This showed that it is the final assembly that is the most important limitation on the biosynthetic process. The assembly process requires several enzyme steps and we have already highlighted one of these, diacylglycerol acyltransferase (DGAT), as being a significant controlling factor. We now wish to examine enzymes, other than DGAT, involved in storage lipid assembly and in supply of component parts. This will enable us to quantify the limitations imposed by different enzymes of the pathway and, furthermore, will provide information to underpin logical steps in genetic manipulation leading to plants with increased oil synthesis and storage capabilities. We will use rape plants where the activity of individual enzymes in the biosynthetic pathway have been changed and quantify the effects on overall oil accumulation. To begin with we will use existing transgenic oilseed rape, with increased enzyme levels, where increases in oil yields have been noted; these are available from our collaborators (Canada, Germany). For enzymes where there are no current transgenic plants available, we will make these and carry out similar analyses. Although our primary focus is on enzymes that increase oil yields, we will also examine the contribution the enzyme phospholipid: diacylglycerol acyltransferase (PDAT) makes to lipid production because this enzyme controls the accumulation of unsaturated oil, which has important dietary implications. In the analogous model plant Arabidopsis, PDAT and DGAT are both important during oil production. Once we have assembled data from these transgenic plants we will have a much better idea of the control of lipid production in oilseed rape. Our quantitative measurements will provide specific targets for future crop improvements. In addition, because we will be monitoring oil yields as well as flux control we will be able to correlate these two measures. Moreover, plants manipulated with multiple genes (gene stacking) will reveal if there are synergistic effects of such strategies. Because no one has yet defined quantitatively the oil synthesis pathway in crops, data produced in the project will have a fundamental impact in basic science. By combining the expertise of three important U.K. labs. with our world-leading international collaborators, this cross-disciplinary project will ensure a significant advance in knowledge of direct application to agriculture.

  • Funder: UKRI Project Code: BB/F015615/1
    Funder Contribution: 715,310 GBP
    Partners: La Trobe University, UBC, BU, USGS Patuxent Wildlife Research Center

    We propose to undertake the first detailed scientific studies into the flight biology, migratory physiology and energetics of bar-headed geese in the wild using the latest electronic dataloggering technology. Ultimately, we will address the question of where are the limits to sustainable avian flight performance at high altitudes and what is the effect of body mass? In particular, how do larger species cope during flight with the combined effects of reduced air density, low oxygen availability and decreased temperature? Only a few species of larger birds are thought to be able to sustain long periods of flapping flight at high altitudes and these have received little study. The best known species is the bar-headed goose (Anser indicus) which performs one of the most physically challenging and impressive avian migrations by flying twice a year through the high plateau areas of the Himalayas, with some populations travelling between high altitude breeding grounds in China and lowland wintering areas in northern India. Despite their extraordinary flight performance and immensely interesting physiology and behaviour, neither the aerodynamic or physiological adaptations required to perform such feats are well understood. We will use miniature GPS tracking devices to provide detailed position and altitude during the flights so that we can identify their route in relation to the geographical topography and environmental conditions. This will also allow us to measure their rates of climb when migrating through the mountains. The bar-headed goose migration is exceptional for such a large bird as aerodynamic and biomechanical considerations suggest that as birds increase in body mass flight performance should deteriorate. Thus, bar-headed geese with a body mass of around 2.5 to 3.5 kg should only have a marginal physical capacity to sustain climbing flight even at sea level, and this ability should get worse as altitude increases due to the decrease in air density. By using 3-axis accelerometry we will be able to calculate the net aerodynamic forces acting on the body of the birds and monitor any changes in wingbeat frequency and relative wingbeat amplitude in response to changes in altitude and during the climbing flight. Their flights are also remarkable due to the physiological difficulties of sustaining any kind of exercise while coping with the harsh environmental conditions of the Tibetan plateau, especially the low ambient temperatures and the reduced availability of oxygen. Nevertheless, bar-headed geese have been recorded to fly between 4,000 m and 8,000 m, where partial pressures of oxygen are around 50% that of sea-level and temperatures can be as low as -20 C. We will measure the heart beat frequency of the birds during flights at different altitudes and estimate the maximum efforts expended during climbing flights in relation to their maximum expected capabilities. To place the remarkable migratory flights of the bar-headed goose in context, some 90% of avian migrations over land occur below 2000 m and the majority below 1000 m, which is well below the level of some of the main breeding lakes of the bar-headed goose (4,200 m to 4,718 m). We anticipate that the geographical barrier of the Himalayas should force these relatively large birds to fly close to the limits of their cardiac, muscular, respiratory and aerodynamic abilities. Indeed, this proposal will address the hypothesis that these migratory climbing flights may only by possible with the assistance of favourable up currents of air due to weather fronts or topographical reflections. Recent developments in electronic dataloggers now make it possible to measure both physical and physiological aspects of flight behaviour in free-flying birds rather than in animals constrained by captive conditions. Access to free-flying bar-headed geese would provide a unique opportunity to study the flight biology of a relatively large bird pushed to the extremes of its performance.

  • Funder: UKRI Project Code: BB/R008035/1
    Funder Contribution: 495,349 GBP
    Partners: SFU, University of St Andrews

    Carbohydrates, or sugars, are ubiquitous throughout nature and perform a number of important functions in our cells. Carbohydrates can exist in long chains, called polysaccharides, which is how energy is stored from the food we eat, why wood is strong and is responsible for the molecular glue that sticks our cells together. At the other end of the scale, single or a few sugars can be appended to other biomolecules such as proteins and lipids and are important in cell processes such as signalling and defence against pathogens. The structure and sequence of carbohydrates is complex and highly variable, but unlike DNA there is no genetic code that can be read to determine how it should exist. Instead, carbohydrate structure and sequence is defined only the enzymes, nature's catalysts, that make and break-down the carbohydrate molecules. We are interested in an enzyme, called HexD, which cleaves a sugar called N-acetyl galactosamine from substrates. Little work has been done to characterise human HexD, and the substrate on which it acts in cells, and its function, are unknown. However, it has been shown that HexD is found in the synovial fluid of patients suffering from rheumatoid arthritis, and thus understanding HexD at the molecular level could have an important impact on the health of patients suffering from the disease in the longer term. Our preliminary work on HexD suggests it may act on proteins in cells, but further investigations are needed to understand this fully. We have also revealed that HexD has some unprecedented activities, which we will dissect. The over-arching aim of the project is to understand the biological role played by HexD, and we will do this by gaining fundamental insights into how HexD works at the molecular level. We will make HexD in the laboratory and study how it works, test various substrates in order to understand its catalytic activities, and identify proteins with which it interacts in cells. We will also develop specific inhibitors against HexD, which will significantly slow its activity. These inhibitors will be administered to cells, and we will examine the effect on how the cells grow and work, to aid our understanding of the role played by HexD. In addition, we will change (increase and decrease) the levels of HexD in cells and similarly monitor the effect. Overall, these experiments will advance our understanding of the biological function of HexD.

  • Project . 2012 - 2014
    Funder: UKRI Project Code: BB/K004204/1
    Funder Contribution: 118,989 GBP
    Partners: SIB, QMUL, OICR

    The hereditary information carried by each living thing is its genome. Stored in the form of the DNA sequences of As, Cs, Gs, and Ts, between 1 and 5% of the genome sequence consists in genes. These genes contain instruction sets for small protein machines that accomplish specific tasks and ultimately determine the organism's shape, size, behavior, lifespan and disease susceptibility. Determining the genome sequence of an organism is now straightforward. But understanding which genes are responsible for the unique characteristics of the organism remains challenging. This is due in particular to the difficulty of correctly finding the genes in the genome and determining which parts of their sequence encode proteins. Indeed, automatic gene identification software performs poorly, thus evidence for each potential gene model needs to be visually inspected and corrected. Thus preparing the data for even a small research project can take months. Luckily there is a solution. Thousands of members of the general public have used the internet to contribute their time to help scientific projects such as GalaxyZoo and FoldIt, be it out of curiosity, desire to help the greater good, gain peer recognition or simply to have fun. Results of their contributions include the identification of previously unknown galaxy types and determination of the 3D structures of AIDS proteins. The proposed project uses a similar approach to encourage members of the general public to help identify genes in the genome and refine their borders. We are constructing a game in which contributors use pattern recognition skills to improve gene models. Contributors will be able to choose to focus their efforts on particular species (e.g.: ants, humans, elephants) or research topics (e.g.: cancer, immunity, longevity, taste or odor perception, behavior). They will earn points and thus peer recognition for their contribtutions, and may be acknowledged in scientific publications or even financially compensated. This project will thus allow members of the general public to have fun while helping to make the world a better place and facilitate scientific discovery.

  • Funder: UKRI Project Code: BB/N00390X/1
    Funder Contribution: 5,400 GBP
    Partners: UQ, McMaster University, University of Warwick, Merck & Co Inc, NOVARTIS

    USA

  • Funder: UKRI Project Code: BB/P025927/1
    Funder Contribution: 28,341 GBP
    Partners: UoC, Aston University

    Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

  • Funder: UKRI Project Code: BB/M026671/1
    Funder Contribution: 241,275 GBP
    Partners: DFO, MSS, AquaGen, UCC, Institute of Marine Research (IMR), UHI, NINA, AgriFood and Biosciences Institute

    Controversy surrounds the actual impacts of Atlantic salmon farming on wild salmonid stocks, fed by the lack of direct evidence for or against many potential impacts, with uncertainty an increasing impediment to sustainable industry development and effective management of wild stocks. This applies to the potential impact of the introgression of farm genomes into locally adapted wild populations from breeding of farm escapes. Escapes do occur and are recognized as inevitable, but are a very small fraction of farm stocks and vary in numbers both locally and temporally. The majority of escapees are expected to die without breeding but some do remain in or ascend rivers and spawn. However, a detailed understanding of actual levels of interbreeding and introgression in most rivers is lacking which, along with an understanding of the adaptive differentiation of farm and wild salmon, is required to establish the actual impact of this potential interaction on the productivity and viability of wild populations. Detection and quantification of interbreeding and introgression requires diagnostic markers for farm and wild genomes. Genetic differentiation of farm and wild genomes can evolve through founder effects, selective breeding and domestication selection and is observed in respect of a variety of molecular markers. However, existing molecular markers are not fully diagnostic and regionally constrained in their usefulness. Unfortunately, marker panels screened for useful variation have been small and arbitrary such that they are unlikely to include the most informative loci and to be context specific, limiting their power and transferability. To properly address the issue of introgression molecular markers are required that are highly diagnostic across all farm and wild populations. These markers will be in genomic regions involved in domestication and controlling the expression of selected economic traits. What is known of the genomic architecture of domestication and most economic traits indicates their control is polygenic, making the targeting of specific gene regions in the search for markers difficult. In contrast, recent advances in genomics make possible genome scanning and genome-wide association studies (GWAS) which can provide a high resolution assessment of molecular differentiation between different individuals or populations across the genome. Different GWAS strategies can be employed but two are deemed optimal in the current context. Firstly, a GWAS will be carried out using a new Atlantic salmon SNP (single nucleotide polymorphism) containing 930k nuclear SNPs, recently developed in collaboration with the salmon farming industry. This will be carried out on a broad base of representative farm and wild stocks. Secondly, GWAS will be carried out to identify temporally stable epigenetic DNA-methylation base changes induced by rearing fish in culture by comparing groups of single source wild fish reared in the wild and in culture. The study will deliver the first general understanding of domestication related molecular genetic differentiation between farmed and wild salmon and identify the best markers for identifying farm salmon in the wild and assessing genetic introgression of farm genes into wild populations. The work will deliver a more robust and generally applicable tool for determining the actual levels of escapes and introgression in wild salmon populations. Following field calibration and independent validation, the diagnostic methodology defined in the study is expected to provide the basis for generating the evidence needed to clarify the debate on levels of escapes and introgression and the long term impacts of introgression on population viability. This will help to define more clearly the path forward for the sustainable development of the salmon farming industry in the UK and elsewhere in the North Atlantic region and help to inform management priorities for wild Atlantic salmon stocks.

  • Funder: UKRI Project Code: BB/L020769/1
    Funder Contribution: 544,176 GBP
    Partners: MRI, University of Sheffield, University of Edinburgh, University of Montreal, Cardiff University

    Life expectancies in the UK have increased rapidly over the last century. If this continues, recent studies have predicted that the majority of babies born since 2000 will live to 100. Our ageing population poses serious economic and medical problems, unless we can find ways of alleviating the process of physiological deterioration and many diseases that are associated with old age. Simple biological measures (or 'biomarkers') capable of illuminating the wider process of ageing and predicting the onset of common diseases of old age could provide important new understanding of the underlying causes of individual variation in ageing rates, as well as interventions to promote healthy ageing. Telomere length (TL) is an exciting candidate biomarker of ageing. Telomeres cap and protect our chromosomes and become shorter with each cell division. When telomeres become very short, cells stop functioning properly, with potentially negative consequences for wider bodily function. Accordingly, the process of telomere attrition is thought to play an important role in the way we age. In humans, telomeres are usually measured in white blood cells, because blood is relatively easy to obtain, and average TL of these cells declines with age. Excitingly, short TL in adulthood predicts various age-related diseases and reduced subsequent survival. However, age only explains a small part of the massive variation in TL among individuals, and we currently do not know why adult TL varies so much. Is it because of genetic or environmental effects on TL at birth, or is it down to differences in growth rates or experiences through early life and adulthood which affect the rate of telomere shortening? To answer this question we need blood samples and information over the entire lifetimes of individuals. This has not been possible in humans because we are so long lived. Furthermore, there are considerable differences in the telomere biology of short-lived and long-lived mammals, so laboratory mice may be poor models for humans. In this project, we will use a remarkably detailed long-term study of Soay sheep on St Kilda to tackle the question of how and why TL varies across the entire lifespan and what this means for the ageing process. It might seem odd to be using wild sheep on a remote island for such a purpose. In fact, the telomere biology of sheep and humans is similar, and the Soay sheep are one of the most closely monitored populations of mammals anywhere in the world. Since 1985, every sheep has been individually marked and followed closely across its lifetime, so we know how quickly they grew, when they bred, where they lived, when they died and we have detailed information on their genetics and the environmental conditions they experience. Importantly, we also regularly re-capture these animals and have collected blood samples repeatedly from around 3000 individuals all the way from birth to death. We will measure TL from archived blood samples to test whether differences in TL in late adulthood are mainly the result of differences in TL at birth or in telomere loss thereafter. We will also test how genes and environment during development influence TL and how natural selection acts on variation in TL. The uniquely detailed, life-long nature of our study will provide the first tests of the causes of individual variation in telomere attrition rates across the entire lifespan of a long-lived mammal. We will also extend the fieldwork on St Kilda to collect samples for more extensive telomere and immunological analyses. Laboratory studies show that a few very short telomeres are enough to compromise cell function, and in white blood cells this could compromise our immune system. Using newly-collected field data and blood samples, we will test both of these predictions outside of the lab for the first time, shedding new light on how changes in TL may influence our ability to fight disease, maintain health and survive in later adulthood.

search
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
15 Projects, page 1 of 2
  • Funder: UKRI Project Code: BB/W010720/1
    Funder Contribution: 3,000 GBP
    Partners: UBC, IFR

    Canada

  • Funder: UKRI Project Code: BB/P02582X/1
    Funder Contribution: 30,612 GBP
    Partners: University of Aberdeen, SFU, MUN, UNIVERSITY OF VICTORIA

    Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

  • Funder: UKRI Project Code: BB/L007320/1
    Funder Contribution: 346,292 GBP
    Partners: NRC, University of Alberta, DuPont (Global), Max Planck, Cardiff University

    Oil crops are one of the most important agricultural commodities. In the U.K. (and Northern Europe and Canada) oilseed rape is the dominant oil crop and worldwide it accounts for about 12% of the total oil and fat production. There is an increasing demand for plant oils not only for human food and animal feed but also as renewable sources of chemicals and biofuels. This increased demand has shown a doubling every 8 years over the last four decades and is likely to continue at, at least, this rate in the future. With a limitation on agricultural land, the main way to increase production is to increase yields. This can be achieved by conventional breeding but, in the future, significant enhancements will need genetic manipulation. The latter technique will also allow specific modification of the oil product to be achieved. In order for informed genetic manipulation to take place, a thorough knowledge of the biosynthesis of plant oils is needed. Crucially, this would include how regulation of oil quality and quantity is controlled. The synthesis of storage oil in plant seeds is analogous to a factory production line, where the supply of raw materials, manufacture of components and final assembly can all potentially limit the rate of production. Recently, we made a first experimental study of overall regulation of storage oil accumulation in oilseed rape, which we analysed by a mathematical method called flux control analysis. This showed that it is the final assembly that is the most important limitation on the biosynthetic process. The assembly process requires several enzyme steps and we have already highlighted one of these, diacylglycerol acyltransferase (DGAT), as being a significant controlling factor. We now wish to examine enzymes, other than DGAT, involved in storage lipid assembly and in supply of component parts. This will enable us to quantify the limitations imposed by different enzymes of the pathway and, furthermore, will provide information to underpin logical steps in genetic manipulation leading to plants with increased oil synthesis and storage capabilities. We will use rape plants where the activity of individual enzymes in the biosynthetic pathway have been changed and quantify the effects on overall oil accumulation. To begin with we will use existing transgenic oilseed rape, with increased enzyme levels, where increases in oil yields have been noted; these are available from our collaborators (Canada, Germany). For enzymes where there are no current transgenic plants available, we will make these and carry out similar analyses. Although our primary focus is on enzymes that increase oil yields, we will also examine the contribution the enzyme phospholipid: diacylglycerol acyltransferase (PDAT) makes to lipid production because this enzyme controls the accumulation of unsaturated oil, which has important dietary implications. In the analogous model plant Arabidopsis, PDAT and DGAT are both important during oil production. Once we have assembled data from these transgenic plants we will have a much better idea of the control of lipid production in oilseed rape. Our quantitative measurements will provide specific targets for future crop improvements. In addition, because we will be monitoring oil yields as well as flux control we will be able to correlate these two measures. Moreover, plants manipulated with multiple genes (gene stacking) will reveal if there are synergistic effects of such strategies. Because no one has yet defined quantitatively the oil synthesis pathway in crops, data produced in the project will have a fundamental impact in basic science. By combining the expertise of three important U.K. labs. with our world-leading international collaborators, this cross-disciplinary project will ensure a significant advance in knowledge of direct application to agriculture.

  • Funder: UKRI Project Code: BB/F015615/1
    Funder Contribution: 715,310 GBP
    Partners: La Trobe University, UBC, BU, USGS Patuxent Wildlife Research Center

    We propose to undertake the first detailed scientific studies into the flight biology, migratory physiology and energetics of bar-headed geese in the wild using the latest electronic dataloggering technology. Ultimately, we will address the question of where are the limits to sustainable avian flight performance at high altitudes and what is the effect of body mass? In particular, how do larger species cope during flight with the combined effects of reduced air density, low oxygen availability and decreased temperature? Only a few species of larger birds are thought to be able to sustain long periods of flapping flight at high altitudes and these have received little study. The best known species is the bar-headed goose (Anser indicus) which performs one of the most physically challenging and impressive avian migrations by flying twice a year through the high plateau areas of the Himalayas, with some populations travelling between high altitude breeding grounds in China and lowland wintering areas in northern India. Despite their extraordinary flight performance and immensely interesting physiology and behaviour, neither the aerodynamic or physiological adaptations required to perform such feats are well understood. We will use miniature GPS tracking devices to provide detailed position and altitude during the flights so that we can identify their route in relation to the geographical topography and environmental conditions. This will also allow us to measure their rates of climb when migrating through the mountains. The bar-headed goose migration is exceptional for such a large bird as aerodynamic and biomechanical considerations suggest that as birds increase in body mass flight performance should deteriorate. Thus, bar-headed geese with a body mass of around 2.5 to 3.5 kg should only have a marginal physical capacity to sustain climbing flight even at sea level, and this ability should get worse as altitude increases due to the decrease in air density. By using 3-axis accelerometry we will be able to calculate the net aerodynamic forces acting on the body of the birds and monitor any changes in wingbeat frequency and relative wingbeat amplitude in response to changes in altitude and during the climbing flight. Their flights are also remarkable due to the physiological difficulties of sustaining any kind of exercise while coping with the harsh environmental conditions of the Tibetan plateau, especially the low ambient temperatures and the reduced availability of oxygen. Nevertheless, bar-headed geese have been recorded to fly between 4,000 m and 8,000 m, where partial pressures of oxygen are around 50% that of sea-level and temperatures can be as low as -20 C. We will measure the heart beat frequency of the birds during flights at different altitudes and estimate the maximum efforts expended during climbing flights in relation to their maximum expected capabilities. To place the remarkable migratory flights of the bar-headed goose in context, some 90% of avian migrations over land occur below 2000 m and the majority below 1000 m, which is well below the level of some of the main breeding lakes of the bar-headed goose (4,200 m to 4,718 m). We anticipate that the geographical barrier of the Himalayas should force these relatively large birds to fly close to the limits of their cardiac, muscular, respiratory and aerodynamic abilities. Indeed, this proposal will address the hypothesis that these migratory climbing flights may only by possible with the assistance of favourable up currents of air due to weather fronts or topographical reflections. Recent developments in electronic dataloggers now make it possible to measure both physical and physiological aspects of flight behaviour in free-flying birds rather than in animals constrained by captive conditions. Access to free-flying bar-headed geese would provide a unique opportunity to study the flight biology of a relatively large bird pushed to the extremes of its performance.

  • Funder: UKRI Project Code: BB/R008035/1
    Funder Contribution: 495,349 GBP
    Partners: SFU, University of St Andrews

    Carbohydrates, or sugars, are ubiquitous throughout nature and perform a number of important functions in our cells. Carbohydrates can exist in long chains, called polysaccharides, which is how energy is stored from the food we eat, why wood is strong and is responsible for the molecular glue that sticks our cells together. At the other end of the scale, single or a few sugars can be appended to other biomolecules such as proteins and lipids and are important in cell processes such as signalling and defence against pathogens. The structure and sequence of carbohydrates is complex and highly variable, but unlike DNA there is no genetic code that can be read to determine how it should exist. Instead, carbohydrate structure and sequence is defined only the enzymes, nature's catalysts, that make and break-down the carbohydrate molecules. We are interested in an enzyme, called HexD, which cleaves a sugar called N-acetyl galactosamine from substrates. Little work has been done to characterise human HexD, and the substrate on which it acts in cells, and its function, are unknown. However, it has been shown that HexD is found in the synovial fluid of patients suffering from rheumatoid arthritis, and thus understanding HexD at the molecular level could have an important impact on the health of patients suffering from the disease in the longer term. Our preliminary work on HexD suggests it may act on proteins in cells, but further investigations are needed to understand this fully. We have also revealed that HexD has some unprecedented activities, which we will dissect. The over-arching aim of the project is to understand the biological role played by HexD, and we will do this by gaining fundamental insights into how HexD works at the molecular level. We will make HexD in the laboratory and study how it works, test various substrates in order to understand its catalytic activities, and identify proteins with which it interacts in cells. We will also develop specific inhibitors against HexD, which will significantly slow its activity. These inhibitors will be administered to cells, and we will examine the effect on how the cells grow and work, to aid our understanding of the role played by HexD. In addition, we will change (increase and decrease) the levels of HexD in cells and similarly monitor the effect. Overall, these experiments will advance our understanding of the biological function of HexD.

  • Project . 2012 - 2014
    Funder: UKRI Project Code: BB/K004204/1
    Funder Contribution: 118,989 GBP
    Partners: SIB, QMUL, OICR

    The hereditary information carried by each living thing is its genome. Stored in the form of the DNA sequences of As, Cs, Gs, and Ts, between 1 and 5% of the genome sequence consists in genes. These genes contain instruction sets for small protein machines that accomplish specific tasks and ultimately determine the organism's shape, size, behavior, lifespan and disease susceptibility. Determining the genome sequence of an organism is now straightforward. But understanding which genes are responsible for the unique characteristics of the organism remains challenging. This is due in particular to the difficulty of correctly finding the genes in the genome and determining which parts of their sequence encode proteins. Indeed, automatic gene identification software performs poorly, thus evidence for each potential gene model needs to be visually inspected and corrected. Thus preparing the data for even a small research project can take months. Luckily there is a solution. Thousands of members of the general public have used the internet to contribute their time to help scientific projects such as GalaxyZoo and FoldIt, be it out of curiosity, desire to help the greater good, gain peer recognition or simply to have fun. Results of their contributions include the identification of previously unknown galaxy types and determination of the 3D structures of AIDS proteins. The proposed project uses a similar approach to encourage members of the general public to help identify genes in the genome and refine their borders. We are constructing a game in which contributors use pattern recognition skills to improve gene models. Contributors will be able to choose to focus their efforts on particular species (e.g.: ants, humans, elephants) or research topics (e.g.: cancer, immunity, longevity, taste or odor perception, behavior). They will earn points and thus peer recognition for their contribtutions, and may be acknowledged in scientific publications or even financially compensated. This project will thus allow members of the general public to have fun while helping to make the world a better place and facilitate scientific discovery.

  • Funder: UKRI Project Code: BB/N00390X/1
    Funder Contribution: 5,400 GBP
    Partners: UQ, McMaster University, University of Warwick, Merck & Co Inc, NOVARTIS

    USA

  • Funder: UKRI Project Code: BB/P025927/1
    Funder Contribution: 28,341 GBP
    Partners: UoC, Aston University

    Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

  • Funder: UKRI Project Code: BB/M026671/1
    Funder Contribution: 241,275 GBP
    Partners: DFO, MSS, AquaGen, UCC, Institute of Marine Research (IMR), UHI, NINA, AgriFood and Biosciences Institute

    Controversy surrounds the actual impacts of Atlantic salmon farming on wild salmonid stocks, fed by the lack of direct evidence for or against many potential impacts, with uncertainty an increasing impediment to sustainable industry development and effective management of wild stocks. This applies to the potential impact of the introgression of farm genomes into locally adapted wild populations from breeding of farm escapes. Escapes do occur and are recognized as inevitable, but are a very small fraction of farm stocks and vary in numbers both locally and temporally. The majority of escapees are expected to die without breeding but some do remain in or ascend rivers and spawn. However, a detailed understanding of actual levels of interbreeding and introgression in most rivers is lacking which, along with an understanding of the adaptive differentiation of farm and wild salmon, is required to establish the actual impact of this potential interaction on the productivity and viability of wild populations. Detection and quantification of interbreeding and introgression requires diagnostic markers for farm and wild genomes. Genetic differentiation of farm and wild genomes can evolve through founder effects, selective breeding and domestication selection and is observed in respect of a variety of molecular markers. However, existing molecular markers are not fully diagnostic and regionally constrained in their usefulness. Unfortunately, marker panels screened for useful variation have been small and arbitrary such that they are unlikely to include the most informative loci and to be context specific, limiting their power and transferability. To properly address the issue of introgression molecular markers are required that are highly diagnostic across all farm and wild populations. These markers will be in genomic regions involved in domestication and controlling the expression of selected economic traits. What is known of the genomic architecture of domestication and most economic traits indicates their control is polygenic, making the targeting of specific gene regions in the search for markers difficult. In contrast, recent advances in genomics make possible genome scanning and genome-wide association studies (GWAS) which can provide a high resolution assessment of molecular differentiation between different individuals or populations across the genome. Different GWAS strategies can be employed but two are deemed optimal in the current context. Firstly, a GWAS will be carried out using a new Atlantic salmon SNP (single nucleotide polymorphism) containing 930k nuclear SNPs, recently developed in collaboration with the salmon farming industry. This will be carried out on a broad base of representative farm and wild stocks. Secondly, GWAS will be carried out to identify temporally stable epigenetic DNA-methylation base changes induced by rearing fish in culture by comparing groups of single source wild fish reared in the wild and in culture. The study will deliver the first general understanding of domestication related molecular genetic differentiation between farmed and wild salmon and identify the best markers for identifying farm salmon in the wild and assessing genetic introgression of farm genes into wild populations. The work will deliver a more robust and generally applicable tool for determining the actual levels of escapes and introgression in wild salmon populations. Following field calibration and independent validation, the diagnostic methodology defined in the study is expected to provide the basis for generating the evidence needed to clarify the debate on levels of escapes and introgression and the long term impacts of introgression on population viability. This will help to define more clearly the path forward for the sustainable development of the salmon farming industry in the UK and elsewhere in the North Atlantic region and help to inform management priorities for wild Atlantic salmon stocks.

  • Funder: UKRI Project Code: BB/L020769/1
    Funder Contribution: 544,176 GBP
    Partners: MRI, University of Sheffield, University of Edinburgh, University of Montreal, Cardiff University

    Life expectancies in the UK have increased rapidly over the last century. If this continues, recent studies have predicted that the majority of babies born since 2000 will live to 100. Our ageing population poses serious economic and medical problems, unless we can find ways of alleviating the process of physiological deterioration and many diseases that are associated with old age. Simple biological measures (or 'biomarkers') capable of illuminating the wider process of ageing and predicting the onset of common diseases of old age could provide important new understanding of the underlying causes of individual variation in ageing rates, as well as interventions to promote healthy ageing. Telomere length (TL) is an exciting candidate biomarker of ageing. Telomeres cap and protect our chromosomes and become shorter with each cell division. When telomeres become very short, cells stop functioning properly, with potentially negative consequences for wider bodily function. Accordingly, the process of telomere attrition is thought to play an important role in the way we age. In humans, telomeres are usually measured in white blood cells, because blood is relatively easy to obtain, and average TL of these cells declines with age. Excitingly, short TL in adulthood predicts various age-related diseases and reduced subsequent survival. However, age only explains a small part of the massive variation in TL among individuals, and we currently do not know why adult TL varies so much. Is it because of genetic or environmental effects on TL at birth, or is it down to differences in growth rates or experiences through early life and adulthood which affect the rate of telomere shortening? To answer this question we need blood samples and information over the entire lifetimes of individuals. This has not been possible in humans because we are so long lived. Furthermore, there are considerable differences in the telomere biology of short-lived and long-lived mammals, so laboratory mice may be poor models for humans. In this project, we will use a remarkably detailed long-term study of Soay sheep on St Kilda to tackle the question of how and why TL varies across the entire lifespan and what this means for the ageing process. It might seem odd to be using wild sheep on a remote island for such a purpose. In fact, the telomere biology of sheep and humans is similar, and the Soay sheep are one of the most closely monitored populations of mammals anywhere in the world. Since 1985, every sheep has been individually marked and followed closely across its lifetime, so we know how quickly they grew, when they bred, where they lived, when they died and we have detailed information on their genetics and the environmental conditions they experience. Importantly, we also regularly re-capture these animals and have collected blood samples repeatedly from around 3000 individuals all the way from birth to death. We will measure TL from archived blood samples to test whether differences in TL in late adulthood are mainly the result of differences in TL at birth or in telomere loss thereafter. We will also test how genes and environment during development influence TL and how natural selection acts on variation in TL. The uniquely detailed, life-long nature of our study will provide the first tests of the causes of individual variation in telomere attrition rates across the entire lifespan of a long-lived mammal. We will also extend the fieldwork on St Kilda to collect samples for more extensive telomere and immunological analyses. Laboratory studies show that a few very short telomeres are enough to compromise cell function, and in white blood cells this could compromise our immune system. Using newly-collected field data and blood samples, we will test both of these predictions outside of the lab for the first time, shedding new light on how changes in TL may influence our ability to fight disease, maintain health and survive in later adulthood.